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Topic Review
GPCRs In Intracellular Compartments: Implications For Drug Discovery
The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional differences between cells. G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors, and their signal transduction is traditionally viewed as a chain of events initiated from the plasma membrane. Furthermore, their intracellular trafficking, internalization, and recycling were considered only to regulate receptor desensitization and cell surface expression. On the contrary, accumulating data strongly suggest that GPCRs also signal from intracellular compartments. GPCRs localize in the membranes of endosomes, nucleus, Golgi and endoplasmic reticulum apparatuses, mitochondria, and cell division compartments. Importantly, from these sites they have shown to orchestrate multiple signals that regulate different cell pathways. 
  • 509
  • 08 Oct 2022
Topic Review
Post-transcriptional RNA Modifications
Post-transcriptional RNA modifications (also called “Epitranscriptomics”) can be detected in RNA while using various methods and approaches exploiting the chemical and physico-chemical properties of these non-canonical RNA nucleotides. 
  • 509
  • 31 Mar 2021
Topic Review
Neutrophil Apoptosis as A Powerful Anti-Inflammatory Signal
Neutrophils are highly abundant circulating leukocytes that are amongst the first cells to be recruited to sites of infection or sterile injury. Their ability to generate and release powerful cytotoxic products ties with their role in host defence from bacterial and fungal infections. Neutrophilic inflammation is tightly regulated to limit the amount of ‘bystander injury’ caused. Neutrophils were in the past regarded as short-lived, indiscriminate killers of invading microorganisms. Neutrophils are recognised to also have important anti-inflammatory functions that are critical for the resolution of inflammation and return to homeostasis.
  • 508
  • 30 Dec 2022
Topic Review
Bile Acids in Alcohol-Associated Liver Disease
Alcohol-associated liver disease (ALD) is a spectrum of diseases, the onset and progression of which are due to chronic alcohol use. ALD ranges, by increasing severity, from hepatic steatosis to alcoholic hepatitis (AH) and alcohol-associated cirrhosis (AC), and in some cases, can lead to the development of hepatocellular carcinoma (HCC). ALD continues to be a significant health burden and is now the main cause of liver transplantations in the United States. ALD leads to biological, microbial, physical, metabolic, and inflammatory changes in patients that vary depending on disease severity. ALD deaths have been increasing in recent years and are projected to continue to increase. Current treatment centers focus on abstinence and symptom management, with little in the way of resolving disease progression. Due to the metabolic disruption and gut dysbiosis in ALD, bile acid (BA) signaling and metabolism are also notably affected and play a prominent role in disease progression in ALD, as well as other liver disease states, such as non-alcoholic fatty liver disease (NAFLD).
  • 508
  • 11 May 2022
Topic Review
TRPV4 Ion Channel
The transient receptor potential vanilloid 4 channel (TRPV4) belongs to the mammalian TRP superfamily of cation channels. TRPV4 is ubiquitously expressed, activated by a disparate array of stimuli, interacts with a multitude of proteins, and is modulated by a range of post-translational modifications, the majority of which we are only just beginning to understand. Not surprisingly, a great number of physiological roles have emerged for TRPV4, as have various disease states that are attributable to the absence, or abnormal functioning, of this ion channel. This review will highlight structural features of TRPV4, endogenous and exogenous activators of the channel, and discuss the reported roles of TRPV4 in health and disease.
  • 507
  • 01 Feb 2021
Topic Review
Aging of Human Hematopoietic Stem and Progenitor Cells
In human blood and immune system, aging is characterized by a decline of innate immunity and regenerative potential of hematopoietic stem cells. This decline is defined at a molecular level in the  hematopoietic stem and progenitor cells (HSPC) compartment. A series of studies have demonstrated that aging of HSPC is induced by an accumulation of senescent cells in the HSPC compartment of the aging human bone marrow. Multi-omics studies have provided evidence that senescent cells are characterized by elevated central carbon metabolism. This property has rendered an enrichment of senescent HSPC for in depth mechanistic studies possible, and in addition has provided novel targets for senolysis therapy strategies. 
  • 507
  • 02 Apr 2022
Topic Review
Subcellular Localization of Membrane-Type-1 Matrix Metalloproteinase
Matrix metalloproteinases (MMPs) are critical enzymes involved in a variety of cellular processes. MMPs are well known for their ability to degrade the extracellular matrix (ECM) and their extracellular role in cell migration. Membrane-type-1 matrix metalloproteinase (MT1-MMP), a transmembrane protein, is first known to localize to the cell membrane.
  • 506
  • 15 Sep 2022
Topic Review
FtsHi Enzymes of Arabidopsis thaliana
FtsH metalloproteases found in eubacteria, animals, and plants are well-known for their vital role in the maintenance and proteolysis of membrane proteins. Their location is restricted to organelles of endosymbiotic origin, the chloroplasts, and mitochondria. In the model organism Arabidopsis thaliana, there are 17 membrane-bound FtsH proteases containing an AAA+ (ATPase associated with various cellular activities) and a Zn2+ metalloprotease domain.
  • 505
  • 15 Jun 2021
Topic Review
Doxorubicin-Induced Mitochondrial Dysfunction
Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. 
  • 505
  • 08 Jul 2022
Topic Review
Contribution of Lactate Metabolism in Cancer Progress
The Warburg effect describes a unique phenomenon that cancers incline to shift the mode of oxidative phosphorylation (OXPHOS) to glycolysis in spite of abundant oxygen. Lactate is the main production of glycolysis, which contains two isomers, L-lactate and D-lactate. The accumulation of high lactate in solid tumors and its extracellular environment is considered as the key and early evidence of malignant development, which is associated with a poor prognosis. Lactate reprograms the tumor microenvironment (TME) to have profound effects on cancer cell phenotype and is conducive to the progress of cancer that involves the eight biological capabilities acquired of cancer: sustaining cell proliferation, promoting growth, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. Lactate’s contribution to cancer is not only the respiratory fuel but also the regulator of intracellular and extracellular molecular signaling in the TME.
  • 505
  • 11 Jan 2023
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